l29 - imrt and igrt for pelvic abdomen cancer - de crevoisier
DESCRIPTION
diabticTRANSCRIPT
IMRT/IGRT for pelvic/abdomen cancer
ESTRO course
R. de CrevoisierCentre Eugène Marquis, Rennes, France
October 2012, New Dehli
IMRT and IGRT for pelvic/abdomen cancer:
1. Prostate cancer: - primary tumor- after prostatectomy
2. Gynaecological cancers: - cervix carcinoma- endometrial cancer
3. Digestive cancer: - anal canal- rectum- pancreas
Exclusion of practical aspects (already presented in clinical cases)
pelvic lymph nodes+++
OUTLINE
IMRT and IGRT for prostate cancer
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
Rational for dose escalation in
prostate cancer
Randomized studies showing the benefit of dose escalation (without IMRT and androgen deprivation)
Randomization
Standard dose (67-70 Gy)
High dose (76-80 Gy)
Randomized studies showing the benefit of dose escalation (without IMRT and androgen deprivation)
Prostate + SV70
80
Intermediate risk306GETUG 06
2010
Prostate + SV(+ AD =143 pts)
68
78
T1b-T4N0(low risk:18%, int:27%, high: 55%)
669Dutch
2008
Prostate + SV
proton
70
79
T1b-2b and
PSA<15
393Zietman
2005
pelvis(46 Gy) + boost70
78
T1-T3305Pollack,,Kuban
2000, 2002, 2008
pelvis(50 Gy) + boost
proton
67
76
T3-4
N0-N2
202Shipley
1995
VolumeDose (Gy)
TumorsNb of Pts
R°
Standard dose (67-70 Gy)
High dose (76-80 Gy)
Local control
(negative biospy)
Freedom from biochemical failure
Freedom from clinical failure
Specific survival
Shipley
1995Gl 8:
19% vs 64%
No PSA available NS NS
Pollack, Kuban
2000, 2002, 200872% vs 65%
NS
PSA<10 NS
PSA>10 p=0.012
7% vs 15%
(p= 0.01)
P<0.05
Zietman
200548% vs 67%
(p<0.001)
61% vs 80%
(p<0.001)
including low risk group
NS NS
Dutch 2008 NS 45% vs 56% (p<0.001),
mainly intermediate risk group
NS NS
GETUG 06
2010NS PSA>15 p=0.03 NS NS
Median folow-up = 10 years
Randomized studies showing the benefit of dose escalation
R°
Standard dose (67-70 Gy)
High dose (76-80 Gy)
Price of non-IMRT dose escalation in prostate cancer ?
IMRT -IGRT in Prostate
Cahlon, Seminars in Radiation Oncology 2008
Randomized studies
GETUG 06 70
80
14
22
NS .0410
18
Cahlon, Seminars in Radiation Oncology 2008
risk of toxicity x2
Strong rational for dose escalation
in prostate cancer however you
will pay a pr ice for it (if no IMRT)
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
Dosimetric benefit of IMRT over 3DCRT
- concave dose distributions
- tight dose gradients
3DCRT
Dosimetric study comparing 3DCRT with IMRT
3DCRT:
2 lat et 4 oblique (310°, 50°, 230°,130°)
Luo, IJROBP 2006
31 pts
T1b-T2c
IMRT:
- 5 beams: 0°, 45°, 135°, 225°, 315°
- 7 beams: 0°, 40°, 80°, 120°, 240°, 280°, 320 °
Target volume : - prostate only (74 Gy)
- prostate (74 Gy) et VS (50 Gy)
BLADDER RECTUM
PROSTATE only
3DRT
IMRT
V60, V70, mean: p<0.05 V60, V70, mean: p<0.05
Luo, IJROBP 2006
BLADDER RECTUM
PROSTATE only
PROSTATE and SV
3DRT
IMRT
V60, V70, mean: p<0.05V60, V70, mean: p<0.05
V60, V70, mean: p<0.05 V60, V70, mean: p<0.05
Dosimetric benefit of IMRT in pelvis
35 pts
large pelvis
(above L5-S1
)
IMRT
3D-CRT
Wang-Chesebro IJROBP 2006
IMRT versus 3D-CRT to treat the pelvis
2 LN target volumes compared (> limit): - small pelvis (L5-S1)
- large pelvis (> L5-S1, lower para-aortic nodes)
2 EBRT techniques compared: - bony landmarks 3DCRT - IMRT
Wang-Chesebro IJROBP 2006
IMRT improves lymph nodes coverage compared with 3DCRT
small pelvis
large pelvis
IMRT decreases dose to critical structures compared with 3DCRT
Wang-Chesebro IJROBP 2006
Wang-Chesebro IJROBP 2006
IMRT decreases dose to critical structures compared with 3DCRT
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
Yes, IMRT decreases significantly
the dose to the rectum, the bladder ,
the bowel and the penil bulb
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
Clinical benefit of IMRT
IMRT =dose escalation toolincreasing biochemical control while not
increasing toxicity
no randomized studies comparing 3DCRT and IMRT
IMRT -IGRT in Prostate
Zelefsky, J Urol 2001
Low risk Intermediaterisk
High risk
86.4 Gy
86.4 Gy
Up to 86.4 Gy !!!
���� 81 - 86,4 Gy
Median follow-up= 24 months (6-60)
Zelefsky, IJROBP 2002
IMRT allows dose escalation while limiting acute toxicity
Alicikus Cancer 2011
170 patients received 81Gy with IMRT
median follow-up =8.2 years
IMRT provides very low GI toxicity despite high dose in the prostate
IMRT decreases GI toxicity compared to 3DCRT (non randomized study)
Zelefsky, J Urol 2001
3DCRT (without IMRT)
IMRT
Dolezel,Strahlenther Onkol 2010
IMRT decreases GI toxicity compared to 3DCRT (non randomized study)
N= 284 pts
- 3DCRT: 74 Gy (n=94)
- IMRT-seq: 78 Gy (n=138)
- IMRT-SIB: 82 Gy (2 Gy) + 73.8 (1.8 Gy) (n=52)
Dolezel,Strahlenther Onkol 2010
IMRT decreases GI toxicity compared to 3DCRT (non randomized study)
Grade 3 late GItoxicity
Cahlon, Seminars in Radiation Oncology 2008
= Low rates of toxicity despite dose escalation in the prostate
Cahlon, Seminars in Radiation Oncology 2008
Toxicity:
Standard dose without IMRT = High dose with IMRT
51 ptsmedian age = 65 years (46–77)
All 18 patients (100%) who were potent post-operatively remained potent after RT(median follow-up = 27 months)
33 pts (64.7%) impotent after nerve-sparingprostatectomy
Bastasch IJROBP 2002, and Teh AJCO 2007
IMRTmean dose = 69.6 Gy (64.0 –72.3)
unilateral or bilateral nerve-sparing prostatectomy
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
Yes, IMRT improves pt outcome
(local control/toxicity) thanks to dose
escalation
(in non randomized studies)
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
Palma IJROBP 2008
10 pts
3DCRT IMRT VMAT
Constant
dose rate
Variable
dose rate
Static-IMRT versus VMAT in prostate ?
5-fields
74 Gy74 Gy
Palma IJROBP 2008
10 pts
Static-IMRT versus VMAT in prostate ?
Palma IJROBP 2008
10 pts
Static-IMRT versus VMAT in prostate ?
Ruchaud, ESTRO 2010
Clinical study
74 Gy in the prostate respecting the dose
constrains in the OAR
Clinical outcome
80 pts
80 pts
Standard IMRT
VMAT
Static-IMRT versus VMAT in prostate ?
Efficiency study
Treatment time/5
Ruchaud, ESTRO 2010
standard
Decrease intrafractional motion ?
Static-IMRT versus VMAT in prostate ?
Clinical study
Ruchaud, ESTRO 2010
CTCAE V3
� acute toxicity: relatively lowand not differentbetween the 2 IMRT modalities
Static-IMRT versus VMAT in prostate ?
--Monitor Units
--Radiation delivery time
++++ (?)+++Dose distribution
VMAT“std” IMRTVMAT“std” IMRT
“Dose optimization”approach
“Time sparing” approach
Tomotherapy
intra-fraction motion / cost
« standard RT protocol » Dose escalation/painting
Static-IMRT versus VMAT in prostate ?
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
IGRT in prostate: strategies
On-line
Prostate (rigid) registration
Indirect prostate visualisation
Fiducials/markers
Direct prostate visualisation
CBCT/Tomotherapy/CT on rails
IGRT in prostate: strategies
On-line
Prostate (rigid) registration (translation)
Indirect prostate visualisation
Fiducials/markers
Direct prostate visualisation
CBCT/Tomotherapy/CT on rails
Adaptive RT
Re-plannning
Prostate rotation
SV volume variations
Ahunbay IJROBP 2010
Modification of multileafcollimator leaf positions using
slice by slice registration
Court IJROBP 2005
Wi Phys Med Bio 2008
Deformableregistration basedre-optimization
IMRT
Adaptive RT: ON-line
Key issue = duration of the re-planning
…realistic ??
IGRT in prostate: strategies
On-line Off-line
Prostate (rigid) registration
Indirect prostate visualisation
Fiducials/markers
Direct prostate visualisation
CBCT/Tomotherapy/CT on rails
« customized »reduced PTV
few 3D imaging (before/during RT)
Adaptive RT
Re-plannning
Adaptive RT: OFF-line
Ghilezan, Seminars RO 2010
During RT
Hoogeman
Radiother Oncol 2005
planning CT + first 4 repeat
CT scans
Before RT
IGRT in prostate: strategies
On-line Off-line
Prostate (rigid) registration (translation)
Indirect prostate visualisation
Fiducials/markers
Direct prostate visualisation
CBCT/Tomotherapy/CT on rails
« customized »reduced PTV
few 3D imaging (before/during RT)
Adaptive RT
Re-plannning
If prostate rotation (outside PTV)
Prostate rotation
SV volume variations
Adaptive RT: hybrid OFF/ON line
Nijkamp IJROBP 2007
-1rst plan:initial 10 mm PTV margin
- new plan:6 CBCT: average CTV and rectum: 7 mm PTV margin
-Weekly CBCT for monitoring
NKI
average prostate position and rectum shape
IGRT in prostate: strategies
On-line Off-line
Prostate (rigid) registration (translation)
Indirect prostate visualisation
Fiducials/markers
Direct prostate visualisation
CBCT/Tomotherapy/CT on rails
« customized »reduced PTV
few 3D imaging (before/during RT)
Adaptive RT
Re-plannning
pre-treatment plan library
(SV)
Prostate rotation
SV volume variations
IGRT in prostate: strategies
On-line Off-line
Prostate (rigid) registration (translation)
Indirect prostate visualisation
Fiducials/markers
Direct prostate visualisation
CBCT/Tomotherapy/CT on rails
« customized »reduced PTV
few 3D imaging (before/during RT)
Adaptive RT
Re-plannning
pre-treatment plan library
(SV)
If prostate rotation
Cumulative dose
(elastic registration)Prostate rotation
SV volume variations
IGRT in prostate: strategies
On-line Off-line
Prostate (rigid) registration (translation)
Indirect prostate visualisation
Fiducials/markers
Direct prostate visualisation
CBCT/Tomotherapy/CT on rails
« customized »reduced PTV
few 3D imaging (before/during RT)
Adaptive RT
Re-plannning
pre-treatment plan library
(SV)
If prostate rotation
Cumulative dose
(elastic registration)
Several IGRT strategies to compensate for
anatomic var iations (from simple to more
complexe)
Does-it translate into clinical benefit ?
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
Random°
Daily IGRT
Day 1,2,3 and weekly IGRT
- Quantification of prostate displacement
-Biochemical and clinicalcontrol /toxicity
- Cost (2D versus 3D and daily versus weekly)
202 pt seach arm (12% difference at 5 years ofbiochemical
control)
IGRT for prostate cancer
De Crevoisier, ASTRO 2009
Preliminary results
Feasibility of prostate registration
- Analysis = 107 pts (410 updated) treated by IGRT = 4078 displacements
- Median total dose = 76 Gy (70-80 Gy)
- IGRT = - Cone Beam CT (67%)- Fiducial markers (28%) - Ultrasounds (5%)
- Prostate registration performed in 94% of cases- Bone registration in 5% of cases
De Crevoisier, ASTRO 2009
Acute toxicity (CTCAE v.3)
Rectal Bladder
Grade 2 7% 36%
Grade 3 0% 4%
De Crevoisier, ASTRO 2009
IGRT reduces rectal toxicity
Chung IJROBP 2008
25 pts
10 pts 15 pts
Reducing margins thanks to IGRT and therefore toxicity
IGRT reduces rectal toxicity
73.8 Gy in the prostate
Chung IJROBP 2008
Dosimetric impact of reducing PTV margin
IGRT reduces rectal toxicity
Chung IJROBP 2008
Dosimetric impact of reducing PTV margin
IGRT reduces toxicity
Acute toxicity
/5-6
Chung IJROBP 2008
PTV < 5 mm ???
- delineation uncertainties
- intra-fraction prostate motion
- uncertainties in registration
Risk of mistargeting and decreased local control ?
Dosimetric impact of reducing PTV margin
IGRT reduces rectal toxicity
Biochemical control by RT technique (Beaumont group, 3064 pts)
Ghilezan, Seminars RO 2010
Clinical benefit of IGRT in prostate
Biochemical control by RT technique (Beaumont group, 3064 pts)
Ghilezan, Seminars RO 2010
Yes, IGRT reduces rectal toxicity and
may improve local control
(although clinical results are still limited)
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?- dose escalation / hypofractionation (SIB) in large target volume
- Toward dose-tumor painting (dominant lesion)
Bayley IJROBP 2009
N=103 pts
-Prostate delineation:CT-MRI co-registration
-IMRT in 2 sequential phases:
- P, SV and LN: 55.1 Gyin 29 fractions of 1.9 Gy
+ consecutive boost in P + SVof 24.7 Gy in 13 fractions of 1.9 Gy (=79.8 Gy)
- IGRT : intraprostatic markers
Bayley IJROBP 2009
IMRT in 2 phases: 55.1 Gy + 24.7 Gy (=79.8 Gy)
median follow-up = 23 months
N=123 pts
Acute toxicity
PELVIC IMRT WITH SIMULTANEOUS INTEGRATED BOOST TO PROSTATE
McCammon IJROBP 2009
30 pts
Intermediate/high riskcancer
Prostate: 70 Gy in 28 fractions (2.5 Gy/fr)
Pelvic LN: 50.4 Gy in 28 fractions (1.8 Gy/fr)
+ androgen suppression
low α/β ratio for prostate cancer (=1.5 to 3)
hypofractionation
77-80 Gy
median follow-up = 24 months (12–43)
McCammon IJROBP 2009
IMRT (high dose with SIB)+IGRT provides low toxicity
HTT very efficient in HTT very efficient in
sparing the IC even at sparing the IC even at
dose levels < 30dose levels < 30--35 Gy. 35 Gy.
Significant sparing of Significant sparing of
rectum and bladder rectum and bladder
even at intermediateeven at intermediate--
low doses (20low doses (20--40 Gy).40 Gy).
Very low incidence Very low incidence
((≤≤ 5%) 5%) of Grade 2 acute of Grade 2 acute
GU and GI TOX. GU and GI TOX.
Disappearance of acute Disappearance of acute
G3 TOX. G3 TOX.
35 ptspelvic LN = 52 Gy
prostate = 74,2 Gy (concomitant boost)
Cozzarini, Fiorino, Radiother Oncol 2007
Intestinal cavity
IMRT -IGRT in prostate
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?- dose escalation / hypofractionation (SIB) in large target volume
- Toward dose-tumor painting (dominant lesion)
230 patients
- Intra-prostatic lesion defined by MRIMRI (pelvic coil+spectroscopic endorectal coil) (+ 4 mm PTV)- Total Dose: - in the prostate =76 Gy in 38 fractions (2 Gy/fr)
- in the IPL= 82 Gy in 38 fractions (2,16 Gy/fr)
Fonteyne IJROBP 2008
Criteria for planning acceptance
230 patients
Total Dose (to the MRI + spectroscopy-detected Intra Prostatic Lesion) =82 Gy
Grade 3 or 4 acute GI toxicity = 0Grade 3 acute GU toxicity = 7%
Fonteyne IJROBP 2008
Prostate registration performed thanks to fiducials
Dose-tumor painting
MRI Planning CT (VMAT) CBCT (IGRT)
Dominant lesion(+ 5mm PTV)
Peripheral zone (+ 5 mm PTV)
Prostate (+ 5 mm PTV)
Jouyaux, Cancer Radiother 2010
Dosimetric study
Dose-tumor painting (VMAT)
High dose in the tumor while respecting the dose constraints in the OARs (no patients treated) Jouyaux, Cancer Radiother 2010
Pinkawa, radiother Oncol 2010
GTV=PET = tumour-to backgroundcholine uptake ratio >2 (studies correlating choline
PET results with histopathologic examinations)
- Prostate = 66.6 Gy in 37 fractions (1.8 Gy/ fr)
- GTV-PET=83.25 Gy in 37 fractions (2.25 Gy/ fr)
(no patients treated)
Pinkawa, radiother Oncol 2010
GTV=PET = tumour-to backgroundcholine uptake ratio >2 (studies correlating choline
PET results with histopathologic examinations)
- Prostate = 66.6 Gy in 37 fractions (1.8 Gy/ fr)
- GTV-PET=83.25 Gy in 37 fractions (2.25 Gy/ fr)
Limiting factor for dose painting
= lack of correlation between imaging (MRI) and
pathology (tumor)
����need for studies
Conclusions: IMRT-IGRT in prostate
1.Total dose in the prostate?
= dose escalation (impact on specific survival)
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
= yes, in all OARs
3. Clinical benefit of IMRT (> standard 3DCRT) ?
= yes, it allows dose escalation without increasing toxicity (no randmzd st)
4. Benefit of arc-IMRT ? Time sparing/ improvement in dose distribution
5. Strategies of IGRT ? = gradient of complexity
6. Clinical benefit of IGRT ? = yes, decrease toxicity
7. IMRT + IGRT opens news approaches:
- dose escalation / hypofractionation (SIB) in large target volume
- toward dose-tumor painting (dominant lesion)
Box technique 3D conformal EBRT IMRT
Years 1990 Years 2000 Years 2010
Arc IMRT
Image-guided RT
Functional imaging (MRI)
Registration tool
Portal imaging
TUMOR DELINEATION
DOSE DISTRIBUTION
TUMOR LOCALIZATION
Dose -guided RT
Dose painting (MRI+VMAT+IGRT)
Hypofractionation
Dose escalation in dominant les
ion
Jouyaux, Cancer Radiother 2010
Respect of the dose contraints in the OAR
IMRT/IGRT for gynaecological cancers
Increasing the dose in the tumor
Decreasing the dose in the OARs
Minimal TOXICITY
Maximal LOCAL CONTROL
IMRT -IGRT in gyn: goal nb 1= decreasing side effects
-Rectum
-Bladder
-Small bowel
-Bone marrow
Late grade 3 complications:- Small Bowel 3%- Rectum 5%- Bladder 5%- Sigmoid < 0.2%
Cervical cancer
Endometrial cancerVulvar carcinoma
Ovarian cancer
Pelvic, inguinal, lombo-aortic
lymph nodes
+ CDDP
Large target volumes +CDDP
> Grade 3 complications = 10-12% at 10 yrs
Why IMRT in gynecological malignancies ?
In the upper pelvis:- the small bowel
- the bone marrow
Roeske, IJROBP 2000
In the lower pelvis:- the rectum
- the bladder
- the bone marrow
In the abdomen:- the kidneys
- the small bowel
To spare:
Increasing the dose in the tumor
Decreasing the dose in the OARs
Minimal TOXICITY
Maximal LOCAL CONTROL
Cervical cancer
Endometrial cancer
Vulvar carcinoma
Ovarian cancer
Pelvic, inguinal, lombo-aortic
lymph nodes
IMRT -IGRT in gyn: goal nb 2=improving local control
To escalate the dose in locally advanced cervical cancer (tumor and nodes)
� PET guided IMRT
Why IMRT in gynecological malignancies ?
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT
(/3DCRT) ?Decreasing the dose in the OARs
Minimal TOXICITY
IMRT in gynaecological tumor
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT ?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the dose to the:
-small bowel
-rectum
-bladder
-bone marrow
-kidney
IMRT in gynaecological tumor
Mundt, IJROBP 2003
36 gynecological tumor pts
IMRT spares the small bowel
DOSIMETRIC STUDY: standard 3DCRT versus IMRT
IMRT
4 fields
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the dose to the:
-small bowel
-rectum
-bladder
-bone marrow
-kidney
IMRT in gynaecological tumor
DOSIMETRIC STUDY: standard 3DCRT versus IMRT
Roeske, IJROBP 2002
10 pts: cervical (5) or endometrial (5)
- CTV: proximal vagina, parametrial tissues, uterus (if present) + regional lymph nodes- PTV: CTV expanded uniformly by 1 cm
4-field box IMRT
45 Gy
average PTV doses: 47.8 Gy 47.4 Gy
IMRT spares the rectum
DOSIMETRIC STUDY: standard 3DCRT versus IMRT
Roeske, IJROBP 2002
average volume of rectum irradiated at the prescription
dose reduced by 23% (p<0.001)
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT ?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the dose to the:
-small bowel
-rectum
-bladder
-bone marrow
-kidney
IMRT in gynaecological tumor
IMRT spares the bladder
DOSIMETRIC STUDY: standard 3DCRT versus IMRT
Roeske, IJROBP 2002
average volume of bladderirradiated at the prescription
dose reduced by 23% (p<0.001)
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the dose to the:
-small bowel
-rectum
-bladder
-bone marrow
-kidney
IMRT in gynaecological tumor
Mell, IJROBP 2008
7 pts
AP/PAIMRT 4 field box
7 pts + CDDP
Mell, IJROBP 2008
Lower pelvic bone marrow
IMRT spares the bone marrow
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the dose to the:
-small bowel
-rectum
-bladder
-bone marrow
-kidney
IMRT in gynaecological tumor
Salama, IJROBP 2006
Extendedirradiation to the para-aortic area
IMRT spares the kidneys
- Significant dose reduction to kidneys- No dose level above 18 Gy
2 fields vs 4 fields vs IMRT
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT
CLINICAL benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT in gynaecological tumor
IMRT in gynecological cancer
Clinical experience relatively limited:
- Limited number of series
- Limited number of pts/series
- Limited follow-up
Increasing the dose in the tumor
Maximal LOCAL CONTROL
CLINICAL benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the toxicity :
- GI toxicity (acute/late)
- GU toxicity (acute/late)
- hematological
IMRT in gynaecological tumor
Hasselle, IJROBP 2011
45 Gy in 1.8-Gy daily fractions
111 patients, 3 institutions (2000-2007), all IMRT
Median follow-up = 27 months
Clinical benefit of IMRT in gynecological cancerLocally advanced cervical cancer
Hasselle, IJROBP 2011
TOXICITY
111 patients, 3 institutions (2000-2007)
Low late toxicity (<3% grade 3 and 4)
Clinical benefit of IMRT in gynecological cancerLocally advanced cervical cancer
Kidd, IJROBP 2010
Clinical benefit of IMRT in gynecological cancer
Locally advanced cervical cancer
GI/GU toxicity
Kidd, IJROBP 2010
non IMRT
IMRT
Clinical benefit of IMRT in gynecological cancer
Locally advanced cervical cancer
IMRT for gynecological tumor is safe: provides high local control and survival
Kidd, IJROBP 2010
Locally advanced cervical cancer
Increasing the dose in the tumor
Maximal LOCAL CONTROL
CLINICAL benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the toxicity :
- GI toxicity (acute/late)
- GU toxicity (acute/late)
- hematological
IMRT in gynaecological tumor
Brixey, IJROBP 2002
Absolute Neutrophil Count36 pts
Pelvic bone marrow
Increasing the dose in the tumor
Maximal LOCAL CONTROL
CLINICAL benefit of IMRT ?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT reduces the toxicity :
- GI toxicity (acute/late)
- GU toxicity (acute/late)
- hematological
IMRT allows new RT indications
IMRT in gynaecological tumor
Recurrence in the para-aortic nodes
Recurrence in the right common iliac lymph nodes
Eifel, IG-IMRT Springer 2006
IMRT for recurrence (re-irradiation)
Rochet, BMC Cancer 2007
-Target volume
whole abdomen + (retroperitoneal, para-aortic and pelvic) nodal areas
-Total dose
30 Gy in 1.5 Gy fractions and 4 weeks(5 × 1.5 Gy per week)
8 pts
IMRT allows to irradiate large volumes
DOSIMETRIC benefit
CLINICAL benefit
Anatomic variations ���� IGRT ?
Cervix and uterus move considerablydue to bladder and rectal filling variations and tumor regression(displacement of the uterine fundus up to 48 mm !!)
IGRT in gynaecological tumor
- For set-up uncertainties= 5-7 mm (Stroom IJROBP 2000)
- For internal organ motion =10-15 mm (Tyagi IJROBP 2011)
�PTV margins should be around 15 mm
(less for the LN=7 mm)
PTV margins
IGRT in gynecological tumors: strategies
EPIDs, kV imaging
Bony anatomy registration(minimize the set-up error)
CBCT, tomotherapyEPIDs, kV imaging
Bony anatomy registration(minimize the set-up error)
Soft tissue visualisation
check the CTV (uterus) inside the PTV
Yes
Treatment
IGRT in gynecological tumors: strategies
CBCT, tomotherapyEPIDs, kV imaging
Bony anatomy registration(minimize the set-up error)
Soft tissue visualisation
check the CTV (uterus) inside the PTV
Yes<
Treatment
No (and systematic)
Increase PTV margins
Off-line:
IGRT in gynecological tumors: strategies
CBCT, tomotherapyEPIDs, kV imaging
Bony anatomy registration(minimize the set-up error)
Soft tissue visualisation
check the CTV (uterus) inside the PTV
Adaptive RT (New plan)
Yes
Treatment
No (and systematic)
Increase PTV margins
Off-line:
IGRT in gynecological tumors: strategies
Stewart IJROBP 2010
2 hypothetical treatment scenarios: - a 3-mm margin plan withno replanning- a 3-mm margin plan with an automatedreplan performed on the updated weeklypatient geometry
Stewart IJROBP 2010
Weeklyreplanning
improves PTV coverage
No replan
Replan
Kerkhof, IJROBP 2008
11 cervical cancer patients
-Contours
-6dose levels:
V10Gy,V20Gy,V30Gy,V40Gy, V42.8Gy,V45Gy10-15 mm1 reference IMRT plan
based on the pre-treatmentMRI scan (pre- IMRT)
-Bladder
- rectum
- bowel
- sigmoid:
4 mm4 weekly IMRT plans per pt, based on weekly MRI scans (to simulate an online-IMRT approach).
ComparisonPTV
(primary and nodal)
IMRT plan
Kerkhof, IJROBP 2008
Online-IMRT in cervix
Kerkhof, IJROBP 2008
Online IMRT compared to pre-IMRT decreases the dose in the OARs(by decreasing PTV margins)
Kerkhof, IJROBP 2008
Online IMRT compared to pre-IMRT decreases the dose in the OARs(by decreasing PTV margins)
Interestin
g in theory but how to do
on-line IM
RT in practice ?
CBCT, tomotherapyEPIDs, kV imaging
Bony anatomy registration(minimize the set-up error)
Soft tissue visualisation
check the CTV (uterus) inside the PTV
Adaptive RT (New plan)
Yes
On-line:
treatment plan library
Treatment
No (and systematic)
Increase PTV margins
Off-line:
IGRT in gynecological tumors: strategies
Predict uterus/cervix shape and positionbased on bladder filling
Bondar, adiother Oncol 2011
2 series of CT-scans
� customized ITV that could replace the conventional PTV
� adaptive strategybased on a pre-treatment generated treatment plan library
IMRT in gynecological cancerConclusions
- IMRT experience is relatively limited (nb of series, nb of pts/series, follow-up)
- IMRT compared to 3DCRT provides:
- dosimetric benefit: in rectum/bladder/small bowel/bone marrow
- clinical benefit:
- is safe
- lower acute +late toxicity (GU/GI/hematological)
- new RT indications: whole abdomen RT / re-irradiation
- IGRT: strong rational due to uterus motion, almost no-clinical experience
Cervix cancer +++
IMRT -IGRT for anal canal
AP/PA 3D-RT IMRT
Menkarios, Radiation Oncol 2007
10 ptsCTV= tumor, anal canal, inguinal, peri-rectal, and internal/external iliac nodes (+ pre-sacral for T4/N2-3)
45 Gy/25 followed by a 14.4 Gy/8 boost
Dosimetric benefit of IMRT in anal canal ?
AP/PA 3DCRT IMRT
>
Menkarios, Radiation Oncol 2007
Dosimetric benefit of IMRT in anal canal
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT
CLINICAL benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT in anal canal tumor
53 ptswith anal cancerIMRT: • 45Gy in: GTV, internal/external iliac + inguinal nodal group • + 9 Gy in primary sites and involved nodes
9 equally spaced fields (0, 40, 80, 120, 160, 200, 240, 280, and320 degrees)
+ cc chemo(5FU /mitomycin C)
Salama
Clinical benefit of IMRT in anal canal
– 58% completed treatment without interruption
– GI toxicity: Grade 3 in 15% with no Grade 4 � Better than RTOG 98-11: 34% had Grade 3 - 4
– Dermatologic: Grade 3 in 38%• Similar to studies with 2-wk treatment breaks� Better than RTOG 98-11: 48%
– Hematologic toxicities: Grade 3 and 4 in 58% of patients� Similar to RTOG 98-11 rates of 60% (however no bone IMRT
constraints)
Salama, JCO 2007
comparison with results from RTOG 98-11 (no IMRT)Concomitant chemo-RT (5-FU/mitomycin) vs.
Induction with 5-FU/Cisplatin followed by concomitant chemo-RT
IMRT in anal canal decreases toxicity
Carcinologic results
– Complete response: 92%– Local recurrence rate:13% @ 18 months– 18-month colostomy free survival: 83.7%– 18-month distant recurrence free survival:92.3%
Salama
IMRT in anal canal is safe
Clivio, Radiother Oncol 2010
10 patients
Plans generated for each case:- fixed beam IMRT- single (RA1) + double (RA2)-modulated arcs
Dose prescription: simultaneous integrated boost:- 59.4 Gy to the primary tumour (at 1.8 Gy/fraction) - 49.5 Gy to risk area including inguinal nodes
Planning objectives:-PTV: minimum dose >95%, maximum dose < 107%-OARs:
- bladder (mean < 45 Gy, D2% < 56 Gy, D30% < 35 Gy)- femurs (D2% < 47 Gy)- small bowel (mean < 30 Gy, D2% < 56 Gy)
Static IMRT versus VMAT in anal canal ?
DOSIMETRIC study
Number of computed MU/fraction:-1531 ± 206 for IMRT- 468 ± 95 for RA1- 545 ± 80 for RA2
Treatment time:- 9.4 ± 1.7 min for IMRT - 1.1 ± 0.0 min for RA1 - 2.6 ± 0.0 min for double arcs
Clivio, Radiother Oncol 2010
Static IMRT versus VMAT in anal canal
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/5
Clivio, Radiother Oncol 2010
Dosimetric benefit of arc-IMRT for the bladder/femurs
IMRT/IGRTin rectal cancer
Dosimetric benefit of IMRT in rectum ?
Mok, Radiation Oncol 2011
10 pts T3 pre-op 45 Gy
Dosimetric benefit of IMRT in rectum
IMRT reduces significantly the dose to the small bowel
Mok, Radiation Oncol 2011
Increasing the dose in the tumor
Maximal LOCAL CONTROL
DOSIMETRIC benefit of IMRT
CLINICAL benefit of IMRT?
Decreasing the dose in the OARs
Minimal TOXICITY
IMRT in rectum tumor
Samuelian, IJROBP 2011
Clinical benefit of IMRT in rectum
50.4 Gy
92 pts
Samuelian, IJROBP 2011
DOSIMETRIC benefit
CLINICAL benefit
Anatomic variations ���� IGRT ?
IGRT in rectum tumor
� mobility + shape variation of the rectum and the mesorectum
(CT scans, CBCT scans, tomographyscans, cine-MRI, clips)
IGRT for rectal cancer
Gwynne Clin Oncol 2011
Lee IJROBP 2006
DEnittisIJROBP 2008
Brierley Ann Oncol 2007
TournelIJROBP 2008
Step 1: quantification of anatomic variations and PTV margins
Anisotropic margins
IGRT for rectal cancer
Gwynne Clin Oncol 2011
Step 2: Define a strategy to correct for the anatomical variations
- Prone position (however set-up variation and discomfort)
- Bony anatomy registration(setup uncertainties)
- Soft tissue visualisation: check the CTV inside the PTV:
-laxatives or rectal enemas(preventive/if distension)
-treatment plan library
-adaptive re-planning
CBCT, tomotherapy
EPIDs, kV imaging
���� Very few clinical results
IMRT for pancreatic tumors
Milano, IJROBP 2004
OARs:
Liver
Kidney
Spinal cord
Small bowel
3D CRT IMRT(7 to 9 fields)
6 pts
CTV:- GTV or tumor bed- draining lymphatics (porta-hepatis, pancreaticoduodenal, celiac, and periaortic)
= 45 to 54 Gy
Dosimetric benefit of IMRT in pancreas ?
Milano, IJROBP 2004
3D4D
IMRT
Dosimetric benefit of IMRT in pancreas
Yovino, IJROBP 2011
46 pts with pancreatic cancer:
IMRT (50.4 Gy) + concurrent chemo((5-FU +capecitabine)
Clinical benefit of IMRT in pancreas
Yovino, IJROBP 2011
46 pts with pancreatic cancer: IMRT (50.4 Gy) + concurrent chemo((5-FU +capecitabine)
� acute GI toxicity compared with those from RTOG 97-04 (3DCRT witout IMRT)
Clinical benefit of IMRT in pancreas
>
IMRT/IGRT in pelvis/abdomen : conclusions
+GI toxicity (acute)- rectum- bladder- bowel- kidney
+pancreas
++++GI toxicity (acute)++rectum
+- GI toxicity- dermato toxicity
- rectum- bladder- bowel- kidney- bone- perineum
++anal canalDigestive
++++endometrium
++++-GU/GI toxicity (acute/late)-hemato toxicity
-local control ?
- rectum- bladder- bowel- kidney- bone- ParaoLN
++cervixGynecol
++++++post-op
++++++++++ pelvic LN
+++ +++++-GU/GI toxicity (acute/late)
- local control
-rectum-bladder-bowel
+++++++« in place »Prostate
ExperienceRationalClinical benefit
Dosimetricbenefit
Experience
IGRTIMRT
Thank you !
Belle Ile, Bretagne, France